Breast cancer, night work and gender inequality in the workplace

Annette LEXA

Doctor in Toxicology EUROTOX

The topic of breast cancer risk in workplace is a neglected subject

While, according to European statistics, approximately 7% of employees in the EU work at night (7.2% in France in 2010), studies on the risk of breast cancer in the workplace receive little attention. There is little scientific literature on this subject. This lack of interest is all the more paradoxical since early detection of breast cancer in women has been the subject of extreme - even meticulous - attention by technocrats and their battalions of territorial health officials since ministerial order of 2006 .

In France, primary prevention in the workplace, improvement of working conditions, occupational medicine monitoring of women at risk (night work, flight attendants) are not part of the cancer plan or the 2006 order 3 .

However, since 2008, night shift work (with irregularly alternating periods of day and night work) has been classified by the International Agency for Research on Cancer (IARC) as a probable human carcinogen. The IARC relied on animal models and epidemiological studies of jetlagged night nurses and flight attendants. These studies show an increased risk of developing breast cancer among these women compared to those who work in conventional workplaces. Night work is thought to disrupt the internal biological clock that regulates the alternation of sleep and wakefulness. In the long term, night-time exposure to light blocks the synthesis of melatonin (sleep hormone) and this leads to a decrease of immune defenses.

It is also thought that this exposure to light could alter the expression of certain genes that can lead to formation of cancer cells. The role of melatonin on estrogens is thought to explain the excess risk of breast cancer 1 and 6. On the other hand, the role of occupational exposures in the development of breast cancer in men (the male individual) has been known for a long time (solvents, ionizing radiation).

Sociologist Marie Ménoret goes further: "Zeneca Pharmaceutical, the world's largest seller of anti-cancer drugs for breast cancer, thanks to its patent for Tamoxifen, is also a producer of pesticides and other deleterious products, known to be carcinogenic. »

According to a study conducted by the Breast Cancer Fund in 2015, the risk of developing breast cancer is increased by 50% among nurses. It is multiplied by 5 in hairdressers and beauticians as well as in the food industry. It is multiplied by 5 among dry cleaning and laundry workers and by 4 among workers in the paper and graphic arts industry as well as in the production of rubber and plastic products. The risk factors are multiple and can be added to each other: job stress is pointed out, night work and frequent time differences, ionizing radiation and chemical substances such as benzene, organic solvents, polycyclic aromatic hydrocarbons, pesticides and many endocrine disruptors poorly or not at all identified by regulations.

A professional prevention for women on the cheap 

In France 2, 61% of employees report being familiar with the CHSCT ( Committee for Safety, Hygiene and Working Conditions) but 62.7% of men compared to only 59% of women. Women are therefore less well informed. Only 35% of male employees are aware of the existence of the risk assessment document, compared with 24% of female employees. This figure must be much lower when it comes to knowledge of the individual exposure form, even though it is mandatory. Worse, being a woman doubles the probability of being overlooked by occupational medicine (probably because it considers that women consult more easily in private practice). And this situation of denial makes the recognition of breast cancer as an occupational disease even more complicated - if not impossible.

"Think Breast Cancer Politically".

The invisibility of specific risks of breast cancer for women in the workplace is a glaring demonstration of the gender inequality of occupational risk prevention policies, while millions of women in Europe, often employed in small, poorly informed and inadequately monitored workplaces, are exposed to chemicals, night shifts, ionising radiation (including in medical diagnosis) and the stress of the double day 5 , which is all the more distressing for women in single-parent families.

To paraphrase Marie Ménoret, breast cancer is definitely a political issue that feminists have totally forgotten to address. The lives of women themselves are at stake. It is urgent that the younger generations take control of it.

References

1/ Travailleurs de nuit : des travailleurs en rupture, HESA Mag n°5 , 1er semestre 2012, 31-35

2/ « Chausser les lunettes du genre » pour comprendre les conditions de travail, Laurent Vigel, HESA mag,N°12, 2e semestre 2015, 12-17

3/ Arrêté du 29 septembre 2006 relatif aux programmes de dépistage des cancers

4/ Ménoret M., 2006, « Prévention du cancer du sein : cachez ce politique que je ne saurais voir », Nouvelles questions féministes, 25(2), 32-47.

5)The average working week for women is 64 hours compared to 53.4% for men. The difference comes from unpaid domestic work (26.4 hours for women compared to 8.8 hours for men).

6/ Document pdf « Travail posté de nuit et cancers » par  M. Druet-Cabanac, Y. Aubert, D. Dumont, Consultation de Pathologies Professionnelles, CHU de Limoges

Cancer Rose est un collectif de professionnels de la santé, rassemblés en association. Cancer Rose fonctionne sans publicité, sans conflit d’intérêt, sans subvention. Merci de soutenir notre action sur HelloAsso.


Cancer Rose is a French non-profit organization of health care professionals. Cancer Rose performs its activity without advertising, conflict of interest, subsidies. Thank you to support our activity on HelloAsso.

Mass screening for breast cancer disregards ethical values and fundamental principles of radiation protection system

By ANNETTE LEXA, Toxicologist PhD

OCTOBER 20, 2019

Mass screening for breast cancer is a technocratic monster inscribed in the law by ministerial order.

It is supposed to be based on the 9 pillars of public health policies. In its wording itself, it flouts the principle of knowledge [1] according to which objectives and actions must take into account the best available knowledge and, conversely, knowledge must meet the need for information to enlighten decisions. However, to date no study has confirmed the effectiveness of screening, based exclusively on the dogma "the earlier a cancer is detected, the better it is cured", which has not been validated in reality as mortality has not decreased since the system was introduced more than 25 years ago.

But it is even worse. The ministerial decree strongly encourages healthy women aged 50 and over to be regularly exposed to ionizing radiation from medical imaging (mammography and synthetic tomography).

The International Commission on Radiological Protection (ICRP) has established principles and values of radiation protection in order to protect populations and individuals [2]. These major principles and values are based on the regulatory use of the linear no-threshold model, which remains a conservative but contested basis [3] in view of recent discoveries in radiobiology. This probabilistic model is based on the dose-response relationship, which postulates that the number of radiation-induced cancers varies linearly with the dose received in an irreversible and cumulative manner and "without threshold" below which an exposure could be considered as having no effect.

Each ionizing particle passing through an organism has a certain probability of hitting the DNA; each impact causes a mutation that has a probability of moving to a stage leading to the initiation of cancerous proliferation. Therefore, overall probability of observing a cancer can only increase linearly with the dose received. Today we know that there is a fundamental inequality between individuals. Each individual has his or her own specific threshold of tolerance to ionizing radiation. Delivering the same dose to all while a non-negligible fraction (5 to 20%) of population has a risk of radiation-induced cancer 10 times higher than the norm is not acceptable. [4]

What are the currently recommended doses?

The recommended doses were enacted in 1991 by the International Commission on Radiological Protection (ICRP). They are valid for entire human population and do not take into account invidual susceptibilities. The commission estimates natural irradiation (radon, telluric, cosmic) at 2.5 mSv/year, average medical irradiation at 1.2 to 2 mSv/year and civil nuclear at 0.2 mSv/year.

Not everyone is equal because there are radon regions and others are not, with radon alone representing 1.2 mSv/year.

In addition, the consumption of medical imaging procedures is exploding with 70 million procedures in France per year (3), and, again for France, the annual dose received for medical diagnosis is 1 mSv/ inhabitant/year on average but can reach 20 mSv/year according to the Academy of Medicine itself, which does not hide its concern [5]. Women undergo more than men, due to the societal obsession with the breast, an accessible but sensitive organ. In the context of breast cancer screening, a woman who is not ill and is still young can also receive a much more radiant tomosynthesis exam, in a doctor's office without being warned of the risk involved. And many women are exposed from the age of 25-30 years by careless practitioners.

For the population, the dose is limited to 5 mSv per year, the maximum tolerable lifetime dose is 70 mSv.

However, doses received during medical imaging exams can lead to an excess of this limit, without taking into account individual susceptibility. For example, the monitoring of scoliosis in young girls in the past generated a dose of 0.11 Sv to the mammary gland.

Perez A-F, et al. Low radiation doses: towards a new reading of risk assessment? Bull Cancer (2015), http://dx.doi.org/10.1016/j.bulcan.2015.03.019

Mammography generates 2 x 2 mGy images spaced 3 minutes apart. Double-strand breaks (DSB) - a source of gene instability leading to the development of cancer - appear as early as 1mGy and the effect is significant around 100-300 mGy. Radiosusceptible individuals with delayed transit of the ATM repair protein simply cannot repair or poorly repair these DSBs in less than 3 minutes, and thus DSBs accumulate during mammography. The risk is all the higher the younger woman is, the more she is unaware of her radiosusceptibility status, and the more the examination is repeated every year or every 2 years. 6] (see the bibliography of Nicolas FORAY's work).

THREE MAIN PRINCIPLES OF THE RADIATION PROTECTION SYSTEM

- The rationale that states that any decision to subject a person to even the weakest possible source of ionizing radiation should do more good than harm. A sufficient benefit must be obtained to offset any costs or negative consequences. Ionizing radiation sources should not be used if there are other alternatives (e.g., no radiography if similar results are obtained with an ultrasound, it is up to physician and radiologist to make the trade-off between benefit and risk, the benefit a person receives from examination must outweigh radiological risk). Practitioners remain primarily responsible for justifying procedures they request or perform.

- The optimization of exposures to these radiations which must be at the lowest possible level;

- The limitation stating that individual exposures must not exceed dose limits recommended by the ICRP in order to avoid occurrence of stochastic (= random) effects. Each country defines regulatory limits based on ICRP recommendations.

ESSENTIAL ETHICAL VALUES UNDERLYING THE RADIATION PROTECTION SYSTEM (2) [7] [7]

Beneficence and non-maleficence 

Beneficence means doing good, and non-maleficence means not doing harm. These two related ethical values have a long history in moral philosophy, going back to the Hippocratic Oath, which requires a physician to do good and avoid harm. The use of radiation, although coupled with certain risks, can undoubtedly have desirable consequences, such as improved diagnosis and cancer therapy in medicine. But these must be weighed against harmful consequences. One of the main challenges in beneficence and non-maleficence is how to measure  benefits versus harm and risks involved. Moreover, such an assessment must be done in a transparent manner.

Prudence

Prudence is the ability to make informed and carefully considered choices in full knowledge of the implications and consequences of actions. It is also the ability to choose and act on what is in our power to do and not do.

Justice 

Justice is generally defined as fairness in distribution of advantages and disadvantages: fair compensation for losses (reparation), fairness of rules and procedures in decision-making processes. First, the principle of fairness in situations reflects personal circumstances in which individuals are involved. This is the role of regulatory dose limits, of compliance with protocols in order to reduce exposures in individuals subjected to the same radiation exposure (see the Toul irradiated persons case).

Inequality can also be seen as the inequity between the doses received by screened non-sick women, especially the youngest, compared to non-sick and unscreened women who are therefore less irradiated.

Dignity

Dignity is an attribute of human condition. It means that every individual deserves unconditional respect, regardless of age, gender, health, social status, ethnic origin, and/or religion. It is the principle of the Universal Declaration of Human Rights which states that all people are born free and equal in dignity and rights.

Personal autonomy is a corollary of human dignity: individuals have the capacity to act freely in order to be able to make informed decisions. This principle is found in "informed consent" in medicine, a principle that states that a person has the right to accept risk voluntarily and has an equal right not to accept it. This informed consent is of paramount importance when it comes to patients who are not seriously ill but are still young and healthy and who are being incited to be screened for cancer and the likelihood of  being affected is very low.

PROCEDURAL VALUES OF THE RADIATION PROTECTION SYSTEM

- Responsibility: individuals responsible for making decisions are accountable for their actions to all those who may be affected by these actions. In terms of governance, this means the obligation of individuals or organizations to account for their activities, to take responsibility and to be prepared to be accountable.

==> The sponsors of the MyPebs study, which aims to recruit women aged 40 and over to compare mass screening with a personalized form of screening, will be accountable in terms of radiation protection and will assume their responsibility when the time comes (and we will make sure they do).

- Transparency means "openness to decisions and activities that affect society, economy, and environment and willingness to communicate them clearly, precisely, quickly, honestly".

Transparency does not simply mean communication or consultation, it means accessibility to information about activities, deliberations and decisions involved and honesty with which this information is conveyed. This transparency implies that all relevant information is provided to persons concerned.

Thus, informed consent has been developed in the context of medical ethics. The prerequisites of informed consent include :

- information (which should be appropriate and sufficient)

- understanding

- volunteering (avoid undue influence)

- all of this associated with the right of refusal and withdrawal (without any prejudice such as the idea that had germinated in the sick brains of a few in the 90s, to withdraw the social rights of women who would not get screened).

For vulnerable people with limited or diminished abilities (people with disabilities, in prison, interned in psychiatric hospitals, etc.), for weak people under the influence of extorting or threatening doctors, for pregnant women, additional protection both in terms of consent and strict evaluation of the benefit/risk ratio is doubly necessary.

However, the 2006 Order [8] (7) went so far as to incite territorial officials to recruit, without information on the radio risk involved, women living in the Guyanese forest, handicapped, in prison, in order to increase the percentage of participation in mass screening for breast cancer, which is an obvious abuse of weakness.

==> By not communicating with women concerned in an honest and transparent manner about the radiation-induced risk and the intrinsic inequality of associated individual risk, mass screening for breast cancer does not respect this ethical value.

Worse, the My Pebs study (https://cancer-rose.fr/my-pebs/), funded by public money at the European level, does not respect this elementary ethical value, since it is to date impossible to freely dispose of the protocol and  women recruited are not informed of the radio-induced individual risk, all the more so as they are younger (inclusion planned from the age of 40).

-Inclusivity 

This is stakeholder participation, which involves all parties concerned in the decision-making processes related to radiation protection.

==> The 2016 citizens' consultation obviously did not respect this fundamental value of radiation protection.

CONCLUSION

By exposing women who are not ill, to ionizing radiation (mammography, tomosynthesis...), mass screening flouts the principles of justification, optimization and limitation of the radiation protection system as they currently exist, i.e. without taking into account individual inequality.

So obsessed with the promise of a fantasized benefit, screening has become blind to the inconsiderate risk it poses to non-ill women by subjecting them to unnecessary examinations, dangerous technologies (tomosynthesis) and without taking into account other possible doses received during the year.

Mass screening - and its uncontrolled extension to young women - flouts the fundamental ethical values of the radiation protection system, which are non-maleficence, prudence, justice (individual inequality in relation to radiation), transparency (lack of communication about individual risk) and inclusiveness in the participation processes.

The same is true of the My Pebs study, which intends to recruit 85,000 so-called "volunteer" women without informing them faithfully of the radiation risk involved, in defiance of the most elementary values of the radiation protection system.

  - But why so much malevolence and so little ethics, we can ask?

    - Because nature hates emptiness,

    - Because idea of doing nothing is unbearable in our mercantile society,

    - Because France hates the idea of citizens having  ability to act freely in order to make informed decisions,

    - Because  lure of gain ignores the principle of non-maleficence, prudence, dignity and equality regarding radio-induced risk.

    - Because there are lobbies (Europa Donna, etc.)

    - Because women have a propensity to subordinate themselves to medical authority from which they are struggling to emancipate themselves, and the market knows it.

Bibliography

[1] Plaidoyer pour l’abrogation de l’arrêté ministériel du 29 septembre 2006 encadrant le dépistage du cancer du sein , Annette LEXA, 2016.

[2] ICRP, 201X. Ethical foundations of the system of 37 radiological protection. ICRP Publication 1XX. Ann. ICRP XX(X), 1–XX.

http://www.icrp.org/docs/TG94%20Draft%20for%20Public%20Consultation%20(20April2017).pdf

[3] https://fr.wikipedia.org/wiki/Lin%C3%A9aire_sans_seuil

   - Argument in favor of the linear no-threshold model: Epidemiological studies have shown an increased risk of cancer at doses of 10 mGy. The carcinogenic effect of doses of the order of 10 mSv is proven in humans. From 10 mGy, the linear no-threshold relationship correctly reflects the dose-response relationship in the Hiroshima and Nagasaki cohort. At doses below 10 mSv, the irradiated cells are crossed by only one trajectory and the effect of each trajectory is an independent stochastic event. The nature of the lesions thus caused and the probability of repair and elimination of the damaged cells do not depend on the dose or the flow rate. The probability that an initiated cell will give rise to cancer is not influenced by lesions in neighboring cells or adjacent tissues.

- Some of the arguments in its favour have lost some of their value, in particular due to numerous results from radiobiology laboratories: Even if ionizations are independent, there may be group effects via cellular communication mechanisms; The efficiency of chromosomal damage repair is directly dependent on the dose rate, with the possibility of hypersensitivity to very low rate radiation; The development of cancer depends not only on an isolated cell but also on the surrounding tissues, which may contribute to its evasion of the immune system; The effects of one irradiation at a given time may depend on previous irradiations (adaptive response).

To these arguments against, we must now add individual susceptibility (genetic and epigenetic) leading a non-negligible part of the population (about 20%) to a risk of radio-induced cancer according to its own tolerance threshold, previously neglected in studies mixing radio-induced and spontaneous cancer with age.

[4] MODULE NATIONAL D'ENSEIGNEMENT DE RADIOPROTECTION DU DES DE RADIOLOGIE, Principes et mise en œuvre de la radioprotection, Drs J.F. Chateil, H. Ducou Le Pointe et D. Sirinelli, 2010. http://www.sfrnet.org/data/upload/files/10_objectifs_et_principes.pdf

[5] De l’usage des Rayons X en radiologie (diagnostique et interventionnelle), à l’exclusion de la radiothérapie. Rapport et recommandations. Dubousset J., Académie Nationale de Médecine, 2016. http://www.academie-medecine.fr/de-lusage-des-rayons-x-en-radiologie-diagnostique-et-interventionnelle-a-lexclusion-de-la-radiotherapie-rapport-et-recommandations/

[6] https://cancer-rose.fr/en/2020/12/29/predictive-test-for-radiotherapy-reactions-women-at-high-risk/

[7] https://cancer-rose.fr/en/2020/12/15/radiotoxicity-and-breast-cancer-screening-caution-caution-caution/

[8] Arrêté du 29 septembre 2006 relatif aux programmes de dépistage des cancers

https://www.legifrance.gouv.fr/affichTexte.do?cidTexte=JORFTEXT000000460656

Cancer Rose est un collectif de professionnels de la santé, rassemblés en association. Cancer Rose fonctionne sans publicité, sans conflit d’intérêt, sans subvention. Merci de soutenir notre action sur HelloAsso.


Cancer Rose is a French non-profit organization of health care professionals. Cancer Rose performs its activity without advertising, conflict of interest, subsidies. Thank you to support our activity on HelloAsso.

Secondary hematological cancers after treated breast cancer

September 19, 2019

Article from January 2019, Summary by Cécile Bour, MD

Evaluation of the Incidence of Hematologic Malignant Neoplasms Among Breast Cancer Survivors in France

JAMA Network Open. 2019;2(1):e187147. doi:10.1001/jamanetworkopen.2018.7147

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6484549/

download PDF 

Authors :

Marie Joelle Jabagi, PharmD, MPH; Norbert Vey, MD, PhD; Anthony Goncalves, MD, PhD; Thien Le Tri, MSc; Mahmoud Zureik, MD, PhD; Rosemary Dray-Spira, MD, PhD

About this study

This is a cohort study. All French women between the ages of 20 and 85 years who were diagnosed with breast cancer and did not die (referred to as "survivors"), between 2006 and 2015, were included and were followed up until the onset of hematological cancer, or until death, or until loss of follow-up, as the case may be. Comparisons were made with all French women in general population enrolled in general health insurance plan each year from 2007 to 2016. Data from the SNDS (containing data from the PMSI and the CepiDC) were analyzed.

Results

The different types of hematological neoplasia considered were acute myeloid leukemia, myelodysplastic syndrome, myeloproliferative neoplasms, multiple myeloma, Hodgkin's lymphoma or non-Hodgkin's lymphoma, acute lymphoblastic leukemia, lymphocytic lymphoma. The incidence (number of new cases) of these different types was estimated and compared to the incidence in women in general population.

In this study of 439,704 French women, women with a diagnosis of breast cancer who had not died from it, had a statistically standardized higher incidence of acute myeloid leukemia and myelodysplastic syndrome compared to women in general population. There was a slight increase in the incidence of multiple myeloma and acute lymphoblastic leukemia.

French women participating in the study who had breast cancer in the last decade were 3X more likely to develop acute myeloid leukemia and five times more likely to develop myelodysplastic syndrome than women in  general population. Several previous studies have linked these pathologies to chemotherapeutic agents, radiotherapy, and taxotere therapy (adjuvant treatment of breast cancer, see HAS 2015 advisory). (See studies [1])

It cannot be ignored that hematological risk of malignant neoplasm reaches peaks within specific time frames after breast cancer.

The annual incidence of acute myeloid leukemia in these patients from this study, increased during the first few years following diagnosis of breast cancer, with an early peak around year three and a subsequent peak around year eight. This finding is consistent with previous studies indicating the presence of 2 types of acute lymphocytic leukemia associated with treatment.

The authors suggest that the latency of onset may depend on the age of the patient at diagnosis, type of therapy and dosage regimen, and also on the limited time of follow-up in the study (even later cases may occur that have not been reported here).

The majority of secondary leukemias are of the myeloid type, but it is estimated that acute secondary lymphoblastic leukemias account for 10% to 12% of all secondary leukemias, with breast cancer being the most common cancer causing these secondary pathologies. In this study, there was a two-fold increase in the incidence of acute lymphocytic leukemia in breast cancer "survivors". Some studies showed that irradiation and chemotherapy were associated with pathogenesis [2], while other studies suggested that prior therapy plays a less important role in secondary acute lymphocytic leukemia than genetic predisposition [3].

A 50% increase in the incidence of multiple myeloma was observed in breast cancer survivors in this study. This slight increase has not been reported and needs to be further investigated, particularly the role of susceptibility due to heredity in BCRA1 and BCRA2 mutation carriers. [4]

Conclusion

This study reveals that acute myeloid leukemia, myelodysplastic syndrome and acute lymphoblastic leukemia are more common in treated women who do not die from breast cancer than in women in the general population; this is of concern and according to the authors, ongoing surveillance of hematological malignancies and further research into the underlying mechanisms of these diseases is needed.

This study is intended to better inform practicing oncologists; patients with a history of breast cancer should be informed of the increased risk of developing certain hematologic malignancies after their first cancer diagnosis.

Recent discovery of genetic signatures that guide treatment decisions in early stages of breast cancer could reduce the number of patients exposed to cytotoxic chemotherapy and its complications, including hematological cancers[5].

It is therefore necessary to continue monitoring trends in the occurrence of hematological cancers, especially as approaches to cancer treatment are evolving rapidly. Further research is also needed to evaluate  treatment modality in cases of genetic predisposition to secondary malignancies.

Comments :

(EDITOR'S NOTE)

Concerns about overdiagnosis are all the more justified because women, some of whom are at high risk and unaware of it [6], may be receiving radiation therapy that they would not have needed, and are being precipitated by screening for a disease they would not have had in its absence, with potential risks inherent in treatment, including secondary hematological diseases.

This has been shown in studies that suggest that risks of treatment may outweigh the expected benefit of screening. [7]

As our dotted poster on the home page of the site (bottom of the page, "poster") shows, the benefit/risk balance in screened women is far from being in favor of benefit, due to overdiagnosis, radiation-induced cancers, radiation-induced coronaritis, surgical and anesthetic accidents, post-treatment thromboembolism, and secondary hematopathies.

The Cancer Rose Collective regrets that these elements are not explicitly detailed in the information brochure given to women who are part of the new study on personalized screening, the MyPebs study. Overdiagnosis is minimized at rates that are currently obsolete, overtreatment, a tangible consequence resulting from overdiagnosis for women, is not stated, and consequences of treatment are not mentioned[8].

References

[1] Studies about relation between breast cancer treatment and Hematologic Malignant Neoplasms:

  • SmithRE,BryantJ,DeCillisA,AndersonS;National Surgical Adjuvant Breast and Bowel Project Experience. Acute myeloid leukemia and myelodysplastic syndrome after doxorubicin-cyclophosphamide adjuvant therapy for operable breast cancer: the National Surgical Adjuvant Breast and Bowel Project Experience. J Clin Oncol. 2003;21 (7):1195-1204. doi:1200/JCO.2003.03.114
  • PragaC,BerghJ,BlissJ,etal.Risk of acute myeloid leukemia and myelodysplastic syndrome in trials of adjuvant epirubicin for early breast cancer: correlation with doses of epirubicin and cyclophosphamide. J Clin Oncol. 2005;23(18):4179-4191. doi:1200/JCO.2005.05.029
  • BeadleG,BaadeP,FritschiL.Acute myeloid leukemia after breast cancer:a population-based comparison with hematological malignancies and other cancers. Ann Oncol. 2009;20(1):103-109. doi:1093/annonc/mdn530
  • Le Deley M-C, Suzan F, Cutuli B, et al. Anthracyclines, mitoxantrone, radiotherapy, and granulocyte colony- stimulating factor: risk factors for leukemia and myelodysplastic syndrome after breast cancer. J Clin Oncol. 2007; 25(3):292-300. doi:1200/JCO.2006.05.9048
  • Galper S, Gelman R, Recht A, et al. Second non breast malignancies after conservative surgery and radiation therapy for early-stage breast cancer. Int J Radiat Oncol Biol Phys. 2002;52(2):406-414. doi:1016/S0360-3016 (01)02661-X
  • RenellaR,VerkooijenHM,FiorettaG,etal.Increased risk of acute myeloid leukaemia after treatment for breast cancer. Breast. 2006;15(5):614-619. doi:1016/j.breast.2005.11.007
  • CurtisRE,BoiceJDJr,StovallM,FlanneryJT,MoloneyWC.Leukemia risk following radiotherapy for breast cancer. J Clin Oncol. 1989;7(1):21-29. doi:1200/JCO.1989.7.1.21

[2]

  • HsuW-L,PrestonDL,SodaM,etal.The incidence of leukemia,lymphoma and multiple myeloma among atomic bomb survivors: 1950-2001. Radiat Res. 2013;179(3):361-382. doi:1667/RR2892.1
  • AndersenMK,ChristiansenDH,JensenBA,ErnstP,HaugeG,Pedersen-BjergaardJ.Therapy-related acute lymphoblastic leukaemia with MLL rearrangements following DNA topoisomerase II inhibitors, an increasing problem: report on two new cases and review of the literature since 1992. Br J Haematol. 2001;114(3):539-543. doi:1046/j.1365-2141.2001.03000.x

[3] GanzelC,DevlinS,DouerD,RoweJM,SteinEM,TallmanMS.Secondary acute lymphoblastic leukaemiais

constitutional and probably not related to prior therapy. Br J Haematol. 2015;170(1):50-55. doi:10.1111/bjh.13386

[4] StruewingJP,HartgeP,WacholderS,etal.The risk of cancer associated with specific mutations of BRCA1and

BRCA2 among Ashkenazi Jews. N Engl J Med. 1997;336(20):1401-1408. doi:10.1056/NEJM199705153362001

[5]

  • CardosoF,van’tVeerLJ,BogaertsJ,etal;MINDACTInvestigators.70-Gene signature as an aid to treatment decisions in early-stage breast cancer. N Engl J Med. 2016;375(8):717-729. doi:1056/NEJMoa1602253
  • SparanoJA,GrayRJ,MakowerDF,etal.Adjuvant chemotherapy guided by a21-gene expression assay in breast cancer. N Engl J Med. 2018;379(2):111-121. doi:1056/NEJMoa1804710

[6]

[7] https://cancer-rose.fr/en/2020/12/29/excess-mortality-due-to-treatment-outweighs-the-benefit-of-breast-cancer-screening-synthesis-of-several-studies/

[8] https://cancer-rose.fr/my-pebs/wp-content/uploads/2019/02/Formulaire-consentement-dorigine.pdf

Cancer Rose est un collectif de professionnels de la santé, rassemblés en association. Cancer Rose fonctionne sans publicité, sans conflit d’intérêt, sans subvention. Merci de soutenir notre action sur HelloAsso.


Cancer Rose is a French non-profit organization of health care professionals. Cancer Rose performs its activity without advertising, conflict of interest, subsidies. Thank you to support our activity on HelloAsso.

Heart disease is the biggest killer of breast cancer survivors

Summary by Cécile Bour, MD

 January 12, 2020

Causes of Death After Breast Cancer Diagnosis: A US Population-Based Analysis

original article Cancer journal

Medscape

The longer  women are followed up after being diagnosed with breast cancer, the more likely it is that a cause of death unrelated to the original cancer would be found. The most common cause of death is heart disease, according to the authors of the study published at the end of 2019 in the journal "Cancer".

The study is based on a population of more than 750,000 American women diagnosed with breast cancer over the past 15 years since the beginning of the century.

The proportion of deaths from non-cancerous causes increased from about 28% in the first year after diagnosis to just over 60% among women who lived for more than 10 years after their breast cancer diagnosis.

These women, having survived their cancer longer, had a significantly increased risk of heart disease and Alzheimer's disease compared to general population.

Results according to monitoring

  • For deaths within 1 to 5 years after diagnosis, breast cancer itself is the responsible cause in the most frequent cases.
  • Among women who died 5-10 years after diagnosis of breast cancer, breast cancer was the cause of death in 38.2%, followed by other cancers in 13.4%, and non-cancerous causes in 48.4%. Heart disease was the most common non-cancer cause of death (15.7%), followed by cerebrovascular disease (stroke) and chronic obstructive pulmonary disease (3.9%) and Alzheimer's disease (3.4%).
  •  In a more distant follow-up, the cardiovascular cause prevails.

Evoked causes

As discussed above, deaths from heart disease and stroke are leading causes of death unrelated to cancer during the post-diagnosis follow-up periods.

But other important causes of death unrelated to breast cancer include chronic liver disease, sepsis, infectious and parasitic diseases. Suicide must also be considered, as it is a significantly higher cause of death than in the general population in all women but particularly among young women.

The high rates of death from heart disease are probably related to the toxicity of chemotherapy (especially anthracyclines) and radiation therapy (especially left breast).

Hypotheses

According to Dr. Sonbol, co-author of the article,

1°Some women could be cured of breast cancer and then die of other intervening causes.

2°For other women breast cancer, e.g. metastatic cancer, may have been transformed into a chronic disease, it may be under control through systematic therapy, and then other causes contribute to death.

Conclusion

According to the authors, these findings provide considerable insight into how patients treated for their breast cancer should receive warnings about future health risks.

Hospital physicians who follow up women that have had breast cancer must work closely with general practitioners to ensure optimal long-term follow-up and prevent various pathologies that may occur during the lifetime of these patients after their treatment.

EDITOR'S NOTE

We would add that overdiagnosis, in this context, must become a major concern, all the more so since it throws healthy women into an illness they should not have known about, and exposes them to these other, potentially serious pathologies which are also likely to seriously impact their lives and lead to death.

Cancer Rose est un collectif de professionnels de la santé, rassemblés en association. Cancer Rose fonctionne sans publicité, sans conflit d’intérêt, sans subvention. Merci de soutenir notre action sur HelloAsso.


Cancer Rose is a French non-profit organization of health care professionals. Cancer Rose performs its activity without advertising, conflict of interest, subsidies. Thank you to support our activity on HelloAsso.

Effect of a mammography screening decision aid for women 75 years of age and older

April 23, 2020

Randomized clinical trial by "cluster" (cluster)

https://jamanetwork.com/journals/jamainternalmedicine/article-abstract/2764100

 Authors: Mara A. Schonberg, MD, MPH; Christine E. Kistler, MD, MASc; Adlin Pinheiro, MA et al.

A cluster randomization trial is a trial in which subjects are randomized not individually but by randomization unit or groups of subjects, known as "clusters".

Here 546 women aged 75 to 89 years, who received a decision aid on mammography screening prior to a health care visit with their practitioner, constitute the randomization unit.

Purpose of the study :

To investigate how the use of a screening decision aid for women 75 years of age and older affects their decision to participate in mammography screening.

Study Results

Providing these women with a mammography screening decision aid prior to their medical visit helps them make informed decisions and leads to fewer women undergoing mammography screening.

Study Conclusion

Therefore a decision support tool can help reduce overscreening.

Our analysis

Cécile Bour, MD

Such a study could be of interest on younger age groups, although an assessment of what concerned women perceive and the impact of the lack of balanced information has already been carried out [1].

How do women perceive the benefits of screening according to what has been conveyed about it, and according to the information they have received, and which has forged their convictions on the subject?
This is the question posed in this study by Domenighetti et al, according to which the table below was drawn up by Nikola Biller-Andorno, a bio-ethics researcher who collaborated on the work of the Swiss Medical Board. [2] [3]

In this comparative table we can find, in part A, data from Domineghetti's American Women's Perception Survey, and in part B, actual data from the most likely scenarios, found from the most convincing and reliable studies. [4]1-3)

The authors (Biller-Andorno et al.) were stunned by the significant discrepancy between women's beliefs about the benefits of screening and the reality, and legitimately asked the question: how could women make an informed decision if the benefits of the procedure were overestimated?

See our article with the detailed results of this work here: https://cancer-rose.fr/en/2020/12/18/perception-and-reality-2/

For the moment, the decision-making tool for women requested by the citizen consultation is completely absent in France, since 2016 when the consultation took place.

There is indeed a question of establishing one " in the French way ", which will hardly be possible given the deficient epidemiological data in our country [5].

Recently in JAMA a viewpoint was published on recommendations for shared decision making with the patient [6].

Unfortunately at the moment it seems that the shared decision is more a medical " dream " than a reality.

Indeed, recommendations from learned societies always have more weight than the values and experiences of the patient, and are sometimes imposed in the media and on patients with great virulence and authoritarianism, as we saw in 2019 with the abusive campaign of the French national college of obstetricians and gynecologists (CNGOF)[7], advocating the extension of screening to the elderly, without any national or international recommendation. The Council of the Order, which we had alerted, did not react ,[8] even though it regularly calls to order those who violate the communication of verified medical notions, as is currently the case in the Covid context.

To conclude

There is still an enormous amount of work to be done so that the values and reality of each patient's life, including her age, can guide the practice of every physician. There is also a long way to go, to ensure that physicians have the practical means to contribute to shared decision making, so that women, both older and younger age groups, finally have access to real tools made on a correct and independent scientific basis.

The development of such tools implies admitting the possibility of women's refusal to participate in screening, as the performance of mammography screening has proven over the decades and in the course of modern studies to be increasingly disappointing.

The real problem is that neither health authorities nor politicians are prepared to accept the possibility of women refusing to be screened for political and ideological reasons, thus depriving them until now of true autonomy in health.

References

[1] Domenighetti G, D'Avanzo B, Egger M, et al. Women's perception of the benefits of mammography screening: population-based survey in four countries. Int J Epidemiol2003;32:816-821 CrossRef | Web of Science | Medline

https://www.ncbi.nlm.nih.gov/pubmed/14559757

[2] https://www.nejm.org/doi/10.1056/NEJMp1401875

[3] https://boris.unibe.ch/51602/7/Biller-Andorno%20NEnglJMed%202014.pdf

[4] 1. Gotzsche PC, Jorgensen KJ. Screening for breast cancer with mammography. Cochrane Database Syst Rev 2013;6:CD001877-CD001877 Medline/

  • Independent UK Panel on Breast Cancer ScreeningThe benefits and harms of breast cancer screening: an independent review. Lancet 2012;380:1778-1786 CrossRef | Web of Science | Medline/
  • Miller AB, Wall C, Baines CJ, Sun P, To T, Narod SA. Twenty five year follow-up for breast cancer incidence and mortality of the Canadian National Breast Screening Study: randomised screening trial. BMJ 2014;348:g366-g366 CrossRef | Web of Science | Medline/

[5] https://cancer-rose.fr/2020/01/22/faisabilite-dun-outil-daide-a-la-decision-sur-le-depistage-du-cancer-du-sein-a-la-francaise-selon-les-criteres-ipdas/

[6] https://cancer-rose.fr/2020/03/14/recommandations-pour-une-prise-de-decision-partagee-avec-le-patient/

[7] https://cancer-rose.fr/2019/04/07/la-campagne-pour-le-depistage-de-la-femme-agee-par-le-college-national-des-gynecologues-et-obstetriciens-de-france-cngof/

[8] https://cancer-rose.fr/2019/05/02/lettre-au-conseil-national-de-lordre-des-medecins-concernant-la-campagne-du-cngof/

Cancer Rose est un collectif de professionnels de la santé, rassemblés en association. Cancer Rose fonctionne sans publicité, sans conflit d’intérêt, sans subvention. Merci de soutenir notre action sur HelloAsso.


Cancer Rose is a French non-profit organization of health care professionals. Cancer Rose performs its activity without advertising, conflict of interest, subsidies. Thank you to support our activity on HelloAsso.

Drop in cancer screening during COVID-19 may aid research on overdiagnosis

An article published on February 11 in the journal STAT tells us about a study project that consists of examining a "natural experiment" to evaluate data such as mortality or overdiagnosis in cancer screening. 

This natural experiment concerns the decline in screening tests during the pandemic. We could then examine and gauge the overdiagnosis of cancers, the real burden of screening, since it throws healthy people into the hell of the disease.

This examination would thus be done at the end of the pandemic, which seems more ethical than a prospective study where patients would have to be randomized in order to be subjected to screening or not.

(Editor's note: however, such a study seems to us to be quite feasible with good information for participants, but more costly and more complicated to set up[1]. It can just be considered that conducting a randomized study on overdiagnosis with two groups of people, perfectly informed before participation in the study, is certainly more ethical than subjecting entire populations, as is currently the case, to highly controversial screenings as to their effectiveness, without any fair information on the benefit-risk balance. This is the case for prostate cancer screening (many men are prescribed a PSA dosage without any explanation) and for breast cancer (many women, uninformed, believe that breast cancer screening is mandatory and will save their lives)).

The author of the article, Ms. E. Cooney, is a general assignment journalist at STAT, a journal of biotechnology, pharmaceutical, policy and life sciences analysis, which she joined in 2017. Previously, she was a blogger at the Boston Globe, before moving to the science editor at the Broad Institute of MIT and Harvard (a biomedical and genomics research center located in Cambridge, Massachusetts, U.S.A.).

Background

Ned Sharpless, current director of the U.S. National Cancer Institute (NCI) and professor of medicine and genetics, was alarmed by the sharp drop in the number of screenings by colonoscopies, mammograms and other cancer screening tests. His concern was motivated by models predicting an explosion in cancer rates if screening was not performed. (In France, we also had our national cancer centres forecasting the worst consequences in the event of non-screening[2]).

However, it will be the delays and postponements in the arrival of patients that will have the most consequences, according to the Grouvid study[3] presented by the statistician Aurélie Bardet of the Gustave-Roussy Institute in Villejuif (Val-de-Marne).

But in January of this year, Mr. Sharpless questioned the downside of early detection: overdiagnosis, when asymptomatic cancers that may not develop and harm the patient are detected, and the overtreatment that accompanies it. The pandemic, he says, could be an opportunity to resolve a long-standing controversy over the extent to which the disadvantages of cancer screening outweigh its benefits. "Knowing the extent to which overdiagnosis and overtreatment actually occur during cancer screening is a very complicated subject," he said. For him, the pandemic has provided an interesting natural experiment, where we could examine some of these tumours, diagnosed later. Is the fate of patients really less favorable because of a later diagnosis of their tumor?

If delays in screening - depending on the cancer and the screening test - do not lead to worse outcomes for most patients, then they could provide valuable information when we will emerge from the pandemic. To demonstrate that non-use of screening is not detrimental, the decline in screening rates should lead to a decrease in overdiagnosis, and not concomitantly result in a significant increase in the number of patients developing disabling or fatal cancers.

(Editor's note: Caution, raw rate data should be examined. In fact, if overdiagnosis could be completely eliminated, the part, i.e., the proportion of serious cancers, would then appear to be greater in the total number of cancers minus overdiagnoses, which usually amplify the total number of cancers. In fact, the proportion of serious cancers is diluted in the total cancer figure when the contribution of overdiagnosis is included in the total cancer figure. 

It is therefore necessary to look at the crude rate and not at the percentage of serious cancers in the total number of cancers identified).

For Mr. Sharpless, the time has come to examine more closely the natural history of cancers during the postponement period, and overtreatments.

Observations already available

For Clifford Hudis, a breast cancer specialist and CEO of the American Society of Clinical Oncology, tests such as colonoscopy are clearly useful. But for other cancers, the impact on survival has been less obvious.
Mr. Hudis emphasizes the difference between screening a person with no symptoms and diagnosing a person with clinical signs. ( It is obvious that under no circumstances consultation should be postponed in case of a clinical symptom).
For him, the evidence is irrefutable: Pap smears and HPV tests to detect precancerous cells in the cervix have significantly reduced mortality rates. Colonoscopy and other screening tests for colorectal cancer in adults have been similarly successful, to the point where an expert panel is recommending screening for colorectal cancer in younger people.
(Editor's note: this opinion is much more nuanced according to experts and studies [4] Perhaps we are still lacking hindsight).

There is much less certainty about the effectiveness of mammography and CT screening for lung cancer, while the use of PSA screening for prostate cancer continues to be controversial[5]. Yet we have "natural experience" with this screening.
Routine PSA testing opened the door to a sharp increase in the incidence of prostate cancer diagnoses, which rose by about 16% per year from 1988 to 1992, then by 9% per year until it stabilized in the late 1990s.
After the U.S. Preventive Services Task Force (USPSTF) changed its recommendation in 2012 to advise men against routine PSA testing, the incidence of prostate cancer has finally stabilized, in contrast to what was happening before widespread testing. And mortality has not changed!

Cooney also relates the position of Barnett Kramer, former director of the NCI's Division of Cancer Prevention: "It's not just prostate cancer where over-diagnosis and over-treatment are a concern," he says. « There are other slow-growing cancers that would never cause suffering during a patient's natural lifetime, and there are also cancers that never progress ».
“You introduce a screening test, in this case for thyroid cancer, kidney cancer, and melanoma, and you dramatically increase the incidence of cancer and prevalence of those cancers,” he declared in front of an association of health journalists.
“There are more and more people that are diagnosed with cancers, and yet you make very little impact on the mortality. They are cured. But they never would have gone on to die of the cancer anyway.”

For instance, while Mr. Kramer sees real harm in overdiagnosis, he does not want this message to encourage people to avoid seeking medical care for symptomatic cancer. “People should be alerted to making sure they seek medical attention at the earliest signs of symptoms,” he said. « We do know that ignoring advancing symptomatic disease is harmful.”

The author also quotes Otis Brawley, former Medical and Scientific Director of the American Cancer Society and now a professor at Johns Hopkins University: “There are cancers that don’t need to be cured. And that’s at least 60% of all prostate cancers and maybe 20% of breast cancers don’t need to be cured.”
(Editor's note: the 20% estimate concerns invasive carcinoma according to the first randomized studies on Canadian trials for example [8], but on the one hand these estimates are now being revised upwards, and on the other hand, if we add carcinomas in situ, 80% of which would not need to be treated, the over-diagnosis of breast cancer is estimated at almost 50%, which means that it could concern one cancer in two detected by mammographic screening [9]).

According to Dr. Sharpless, most cancers are discovered following the appearance of symptoms.
Nevertheless for him “there are plenty of people alive today because they had an asymptomatic lesion detected on some screening exam that was removed, resected, treated, and they’re cured of what would’ve been a very symptomatic cancer. The opposite argument is true, too.”, meaning: many of the living people treated by removing, resecting lesions that would never have become symptomatic.

Another factor to consider is that cancer therapies have improved. Some may be diagnosed at a later stage with delayed screening, but they are curable with effective therapies," says Sharpless. So the higher grades can be apprehended by new therapeutic approaches.

(Editor's note: P. Autier's study noted: The influence of mammography screening on mortality declines with the increasing effectiveness of cancer therapies.)

Which method for evaluation?

Eric Feuer, founder and leader of the NCI Cancer Surveillance Modeling Network Evaluation Project, has worked on NCI models predicting excess mortality from breast and colorectal cancer due to delayed screening. 
He stated that the widespread use of the PSA test was also a natural experiment.
“When screening goes up rapidly, you’re taking cases from the future,” Feuer said. « Some of those cases never would have caused symptoms, but they made incidence rise. The problem is that the PSA test doesn’t accurately predict which cancers, with or without symptoms, will be harmful and which won’t. »

For breast and colorectal cancer, Dr. Feuer will examine data from the Surveillance, Epidemiology, and End Results program (SEER) and other NCI data to see if the decline in screening rates has been followed by a decline and then an increase in incidence. He will monitor rates of positive screening tests, the stage of confirmed cancer diagnosis, and mortality data.
In addition to the SEER, the Population-based Research to Optimize the Screening Process (PROSPR) observational database will also be used to discern the effects that decreased cancer screening may have on the stage at which cancer is diagnosed, among other measures.

All this is supposed to allow the estimation of overdiagnosis, if the data return is powerful enough.

Mr. Kramer (former director of the NCI's Division of Cancer Prevention) has requested that PSA be removed from his usual blood test panel.

Professor Brawley (Johns Hopkins University professor) thinks Covid-19 is the imminent danger we should consider now. His hospital has cancelled elective operations, including radical prostatectomies.

The natural experiment on screening tests will take some time to show results.

“We’ll know in 10 years,” NCI’s Feuer said.

Meanwhile....

The director of the Canadian Breast Imaging Society said her group already has a study underway. The full transcript of the interview can be found at this link: https://www.cbc.ca/radio/thecurrent/the-current-for-feb-9-2021-1.5906730/february-9-2021-episode-transcript-1.5907645

MATT GALLOWAY: Tell me more about that. I mean, in the six months that this pandemic would have perhaps derailed or slowed down or stopped screening, what would be the change in that in terms of, you know, where cancer might be, but also, as you say, survival rates?

JEAN SEELY: Well, it's too early for us to know. And we're starting a study to look at this because we believe that this is a factor that's happening across the country. There was a modelling study done by the group at Sunnybrook, and they used a mathematical model called OncoSim, where they estimated that a six-month delay in screening would lead to 670 more advanced breast cancers in Canada and 250 more breast cancer deaths in the next 10 years. And delaying that even more than six months, which may happen with people stopping or naturally not referring themselves, would lead to an even higher number of deaths. So we are seeing this across the country.

So we can easily imagine how breast medical imaging experts will design the research to their advantage, and how they will promote it. The debate will never end, and a battle of "models" will be engaged.

Opinion of Dr. Vincent Robert, our medical statistician :

"Apart from the fact that this is only a model (and with another model we would certainly find something else), which statistician, and with which tool, would be able to spot an increase of 250 deaths among the random fluctuations of the annual number of deaths (with 12000 deaths per year on average, the confidence interval of the annual number of deaths in France has an amplitude of about 500 deaths, i.e. the annual number of deaths naturally fluctuates by much more than 250; or, if you prefer, an increase of 250 deaths will not appear to be statistically significant). "

To be continued..…

References

[1] https://cancer-rose.fr/my-pebs/methodologie/ - choose article: "l'étude dont on rêvait"

[2] https://cancer-rose.fr/2020/10/06/langoisse-des-thuriferaires-du-rose-face-a-la-decroissance-de-participation/

[3] https://cancer-rose.fr/en/2021/01/18/covid-19-pandemic-and-cancer-management/

[4] https://bmjopen.bmj.com/content/9/10/e032773

[5] https://cancer-rose.fr/en/2021/02/11/parallel-to-breast-screening-prostate-screening-overdiagnosis-as-well/

[6] https://cancer-rose.fr/en/2021/02/01/overdiagnosis-of-thyroid-cancer-another-womans-concern/

[7] https://www.youtube.com/watch?v=068KMIe-gys&feature=emb_logo
Dr. Adewole Adamson's observation is frightening: no reduction in mortality and massive overdiagnosis due to the fact that the tolerance thresholds of dermatologists and anatomo-pathologists are lowered in front of skin lesions.

Dermatologists are increasingly and rapidly asking for biopsies, while anatomical pathologists prefer to upgrade their diagnosis of lesions examined under the microscope (i.e., when in doubt, classify as malignant lesions that are simply dubious and that could only be monitored), giving rise to an apparent melanoma epidemic with even more artificial "survivors".The vicious circle is endless, prompting patients and doctors to do more and more routine skin examinations.

[8] https://cancer-rose.fr/en/2021/01/06/miller-study/

[9] https://cancer-rose.fr/en/2020/12/17/mammography-screening-a-major-issue-in-medicine/

Cancer Rose est un collectif de professionnels de la santé, rassemblés en association. Cancer Rose fonctionne sans publicité, sans conflit d’intérêt, sans subvention. Merci de soutenir notre action sur HelloAsso.


Cancer Rose is a French non-profit organization of health care professionals. Cancer Rose performs its activity without advertising, conflict of interest, subsidies. Thank you to support our activity on HelloAsso.

Being a woman and smoking: radiation in perspective

Lung cancer screening by low-dose CT scan, or the history of a pre-announced disappointment.

In February 2020, a medical imaging  journal[1] triumphed in publishing the results of a clinical trial on lung cancer screening by low-dose chest CT, which was then widely reported in press, promoting this high technology as a systematic screening method in smoking population.

This is a scanning technique using low doses, similar to those delivered by a simple chest X-ray (in two incidences, face and profile, equivalent to 20-40 µSv, instead of 5.8 mSv for a standard chest CT), giving a slightly more degraded image, not very efficient for the analysis of interstitial pneumopathies, but sufficient for a diagnosis of small nodules.

The article in this review concluded as follows: "This study therefore seems to be in favor of organized lung cancer screening, at a time when the procedures have reached very low irradiation levels".

But what is it actually about?

Essentially two trials (there have been several studies) are supposed to provide evidence of a significant decrease in specific mortality from bronchopulmonary cancer. These are the US National Lung Screening Trial (NLST), and the NELSON trial conducted in Belgium and the Netherlands.

Already in 2014, in a guidance brief, the HAS [2] noted: ".... it is likely that the low specificity of low-dose CT screening will remain a major obstacle to the implementation of screening in clinical practice and of a screening program".
"Disadvantages and risks associated with low-dose CT screening include radiation exposures ranging from 0.61 to 1.5 mSv, a certain degree of over-diagnosis that varies between studies, and a high rate of false positive tests, usually explored with more imaging".

When we examine the study published in the NEJM [3] on the NELSON trial, the last line of Table 4 reads as follows: All-cause mortality - deaths per 1000 person-yr 13.93 (screening group) 13.76 (control group) RR 1.01 (0.92-1.11).
This clearly means that there is no impact on all-cause mortality, and this is the only data that should be of interest to the public and the media when reporting the results of such a study.

Remember that the "overall mortality" data includes everything, cancer, its treatment and its non-treatment, and reflects more adequately the "real life" data.
This information is rarely put forward, as the promoters of screening preferentially report the gain in terms of specific mortality, i.e. by the disease alone [4].

But the Academy of Medicine has retained it, and in a published report it expresses its concerns [5] [6]. The Academy notes several problems that prevent this screening from being generalized:

    - The two main trials on lung cancer screening with low-dose CT scans greatly underestimated potential harmful effects (false positives, over-diagnosis, false negatives, irradiation and over-treatment). The magnitude of  benefit and risks are unknown, and even if a 25% cure rate is achieved among subjects included in the study, the majority of patients will die early from other smoking pathologies (other cancers, heart disease, emphysema etc...) without increasing their life expectancy.

- For a screening to be effective, it is necessary to have cancers with a sufficiently long latency to be caught during a screening test (therefore as few interval cancers as possible); yet the proportion of cancers with a long latency in the lung is low.

-"These cancers are mainly due to active smoking and, marginally, to passive smoking: more than 85% of cases can be attributed to tobacco. The progressive decrease in smoking among men (from 60% of smokers in the 1960s to 33% currently) is reflected in the decrease in incidence and mortality due to these cancers", which is equivalent to saying that this cancer is simply accessible to effective primary prevention campaigns and incentives to stop the main risk factor, tobacco.

"The natural and evolutionary history of the disease must be known and the various forms defined"." Between ages of 50 and 74, lung cancers are therefore mainly composed of adenocarcinomas, which seem to be the most easily detectable. For example, in the European NELSON trial, 61% of cancers in the screened group are adenocarcinomas compared to 44% in the control group, which could explain a better effect of screening in women," explains the Academy.

    - Unknowns: on target population, on appropriate participation rate, frequency of scans, therapeutic indications for cancers discovered during the scan, acceptability by patients, motivation and compliance with smoking cessation, etc...

    - People who participate in the trials are not representative of entire population eligible for screening at a later date, which may lead to an overestimation of efficacy in the Nelson study.

    - Economic evaluation is also necessary, with the Academy correctly pointing out that primary prevention is certainly more effective and less costly.

To rebound on the arguments of the Academy of Medicine, it is necessary to bear in mind economic stakes of this screening, not only of the initial examination but also the high cost of iterative examinations in case of intermediate nodules (which must be followed over years to monitor their evolution). Bronchial cancer screening by CT would be 4 times more expensive than breast cancer screening and 10 times more expensive than colorectal cancer screening.

Specifically concerning women

The results on the effectiveness of low-dose CT screening at 10 years are more variable and difficult to interpret in women. The Academy also has reservations, particularly in the NELSON trial, pointing out that they are not significant because of the small number of women included in the two trials and followed up in 10 years.

For our part, we emphasize that this screening, if it is launched in the female smoking population, will be superimposed on the biennial mammography, again in total ignorance of the effect of cumulative doses of iterative examinations [7] [8] for an unproven reduction in mortality [9].

Irradiation draws attention again

Once again, and just as for breast cancer screening, let's keep in mind that we are inflicting radiation, even in low doses, on people who have no complaints, who are a priori healthy, and this radiation will be repeated.

For suspicious (5 to 10 mm) and undetermined nodules, a check-up will be carried out at 3 months. Nodules that increase in volume (+ 25% in volume in 3 months) and nodules larger than 10 mm must be investigated immediately (biopsy or surgery). Stable nodules will be controlled for 3 years.

Some semi-solid nodules may be slow-growing and will be followed for a longer period of time, for 5 years.

All this for a zero gain in terms of overall mortality.

Ionizing radiation induces two types of effects: "deterministic effect", i.e. conditioned directly and with certainty according to the dose of radiation received, for example if a certain threshold is exceeded as in the case of a nuclear catastrophe or during radiotherapy treatments.

The other effect is "random" (appearance of cancers with a certain probability for an individual but without certainty, without a known threshold, depending on individual radiosensitivity).

For diagnostic radiology, the doses used are certainly much lower compared to radiotherapy, but the exposure, especially repetitive, could be harmful in a "probabilistic" way, by an accumulation of alterations of cellular DNA and individual sensitivity. Since most estimates are based on extrapolations of risks observed from nuclear and atomic accidents, long-term effects of even minimal and repeated doses are certainly very variable depending on the individual, and definitely still unknown at the present.

On this subject, read the work of N. Foray, radiobiologist, INSERM.

https://www.sfmn.org/drive/CONGRES/JFMN/2016%20GRENOBLE/SCIENTIFIQUE/CommunicationsOrales/N._FORAY_MembreWeb.pdf

et https://its.aviesan.fr/getlibrarypublicfile.php/cd704e89988a4e3bcf2e1217566876cf/inserm/_/collection_library/201800012/0001/J1-098ITS-2017.foray.lyon.ITMO.TS..21.nov.2017.pdf.pdf

To conclude

For academics, the most important thing is the fight against the main risk factor: smoking, and acceptance of its reduction is the very condition for candidates selected for eventual regular screening.

Chest CT scans could then serve as a motivation for smoking patients to make a decision to quit.

It will then no longer be a matter of systematic screening of an entire population, but rather of using imaging as part of a smoker's health check-up, and as part of the singular colloquium within the medical consultation.

Finally, in the context of recognized occupational exposures, low-dose chest CT scans could be a method of monitoring exposed subjects.

Reactions

They were not long in coming, an APM dispatch of February 24, 2021 informs us that three learned societies are taking a stand.

"The three learned societies are the Francophone Thoracic Cancer Intergroup, the French Lung Society and the Thoracic Imaging Society.

In this text, which updates previous recommendations, the learned societies reaffirm their position in favor of individual screening by low-dose thoracic CT scan without injection of contrast agent, for which they specify the modalities." ......
" Contrary to the Academy of Medicine, which proposes a low-dose scanner once, during a smoker's health check-up, learned societies envisage a recurrent examination. They believe that there should be 2 CT scans one year apart and then one every 2 years, except in the case of risk factors or a previous exam with an intermediate result or it should continue every year.
And this screening should be continued "for a minimum period of at least 5.5 to 10 years".

Again, we note the regrettable and not very scientific reaction of the president of the National Federation of Radiological Doctors:

His text :

"Incompetence or senility? The National Academy of Medicine has rendered a verdict against the use of low-dose CT scanners for the detection of bronchopulmonary cancer. The scanner would contribute to the health assessment of smokers and help them quit smoking."

A new study

https://pubmed.ncbi.nlm.nih.gov/35040922/#:~:text=Conclusions%20and%20relevance%3A%20This%20population,indolent%20early%2Dstage%20lung%20cancers.

This population-based ecological cohort study found that screening for low-dose CT scans of low-risk Asian women, mostly non-smokers, was associated with significant over-diagnosis of lung cancer. Five-year survival is biased by the increased detection of indolent lung cancers at an early stage.
Unless randomized trials can demonstrate some value for low-risk groups, low-dose CT screening should remain targeted only at heavy smokers.

References

[1] http://www.thema-radiologie.fr/actualites/2592/l-etude-nelson-promeut-le-depistage-du-cancer-du-poumon-par-scanner.html

[2] https://www.has-sante.fr/upload/docs/application/pdf/2014-12/note_de_cadrage_cancer_du_poumon.pdf

[3] https://www.nejm.org/doi/full/10.1056/NEJMoa1911793

[4] This "gain" is often expressed as a relative reduction in the risk of dying, i.e. by comparing a screened group with an unscreened group.

In the case of breast cancer, the manipulation is to express this gain repeatedly, in particular in the media, in percentages. Thus you are told that breast cancer screening reduces mortality by 20%, everyone understands that 20 people out of every 100 screened die of this cancer, but this is not the case, in absolute figures there is only one life saved. Out of a group of 2000 women screened in 10 years, there is one death from breast cancer, out of a group of 2000 women not screened in 10 years, there are 5 deaths, the reduction from 5 to 4 is indeed a reduction of 20%, but in real life, it is only one person.…

[5] https://www.academie-medecine.fr/le-depistage-du-cancer-du-poumon-par-scanner-thoracique-faible-dose-stfd-reste-non-justifie-mais-peut-etre-utile-pour-un-bilan-de-sante-des-fumeurs/

[6] https://cancer-rose.fr/wp-content/uploads/2021/02/RAPPORT-Académie-de-médecine.pdf

[7] http://agora.qc.ca/documents/radiation_des_depistages_aux_accidents_nucleaires

[8] https://cancer-rose.fr/en/2020/12/15/radiotoxicity-and-breast-cancer-screening-caution-caution-caution/

[9]https://cancer-rose.fr/2019/10/20/le-depistage-de-masse-du-cancer-du-sein-bafoue-les-valeurs-ethiques-et-les-principes-fondamentaux-du-systeme-de-radioprotection/

Cancer Rose est un collectif de professionnels de la santé, rassemblés en association. Cancer Rose fonctionne sans publicité, sans conflit d’intérêt, sans subvention. Merci de soutenir notre action sur HelloAsso.


Cancer Rose is a French non-profit organization of health care professionals. Cancer Rose performs its activity without advertising, conflict of interest, subsidies. Thank you to support our activity on HelloAsso.

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Cancer Rose est un collectif de professionnels de la santé, rassemblés en association. Cancer Rose fonctionne sans publicité, sans conflit d’intérêt, sans subvention. Merci de soutenir notre action sur HelloAsso.


Cancer Rose is a French non-profit organization of health care professionals. Cancer Rose performs its activity without advertising, conflict of interest, subsidies. Thank you to support our activity on HelloAsso.

Mechanisms of breast cancer

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Cancer Rose est un collectif de professionnels de la santé, rassemblés en association. Cancer Rose fonctionne sans publicité, sans conflit d’intérêt, sans subvention. Merci de soutenir notre action sur HelloAsso.


Cancer Rose is a French non-profit organization of health care professionals. Cancer Rose performs its activity without advertising, conflict of interest, subsidies. Thank you to support our activity on HelloAsso.

Women and health Bruxelles

Women and health. Screening, overdiagnosis, cancer, what are we talking about ?

Bernard Duperray, MD, Radiologist

Evening conference "Informed, free and united in the face of breast cancer screening" , Association « Women and Health », Bruxelles, Novembre, 7, 2019

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Cancer Rose est un collectif de professionnels de la santé, rassemblés en association. Cancer Rose fonctionne sans publicité, sans conflit d’intérêt, sans subvention. Merci de soutenir notre action sur HelloAsso.


Cancer Rose is a French non-profit organization of health care professionals. Cancer Rose performs its activity without advertising, conflict of interest, subsidies. Thank you to support our activity on HelloAsso.

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